1. Field of the Invention
The present invention relates to transdermal electrotransport drug administration devices and, more particularly, to a patch system which includes a current generator and a patient activity sensor for feedback control of the rate of drug delivery.
2. Description of the Prior Art
Transdermal electrotransport is a method of applying a medication to a patient through the application of an electromotive force to drive chemicals through the skin. The electrotransport application of medicaments avoids many problems associated with the percutaneous delivery of drugs. Experimentation has been directed to, development of drugs suitable for electrotransport, and to patch electrode systems suitable for dispensing those drugs.
In general, there are two mechanisms for electrotransport. Iontophoresis generally refers to the transport of charged substances, while electrosmosis refers to the transdermal flux of a liquid solvent (e.g., the liquid solvent containing the uncharged drug or agent) which is induced by the presence of an electric field imposed across the skin by the donor electrode. As used herein the terms "iontophoresis" and "iontophoretic" refer broadly to either, the delivery of charged drugs or agents, the delivery of uncharged drugs or agents by the process of electrosmosis, or both.
The expressions "drug" and "therapeutic agent" are used interchangeably and are intended to have their broadest interpretation as any therapeutically active substance which is delivered to a living organism to produce a desired, usually beneficial, effect. In general, this includes therapeutic agents in all of the major therapeutic areas including, but not limited to, anti-infectives such as antibiotics and antiviral agents, analgesics and analgesic combinations, anesthetics, anorexics, antiarthritics, antiasthmatic agents, anticonvulsants, antidepressants, antidiabetic agents, antidiarrheals, antihistamines, antiinflammatory agents, antimigraine preparations, antimotion sickness preparations, antinauseants, antineoplastics, antiparkinsonism drugs, antipruritics, antipsychotics, antipyretics, antispasmodics, including gastrointestinal and urinary, anticholinergics, sympathomimetrics, xanthine derivatives, cardiovascular preparations including calcium channel blockers, beta-blockers, antiarrythmics, antihypertensives, diuretics, vasodilators, including general, coronary, peripheral and cerebral, central nervous system stimulants, cough and cold preparations, decongestants, diagnostics, hormones, hypnotics, immunosuppressives, muscle relaxants, parasympatholytics, parasympathomimetrics, proteins, peptides, psychostimulants, sedatives and tranquilizers.
The invention is also useful in the controlled delivery or peptides, polypeptides, proteins and other macromolecules. These macromolecular substances typically have a molecular weight of at least about 300 daltons, and more typically a molecular weight in the range of about 300 to 40,000 daltons. Specific examples of peptides and proteins in this size range include, without limitation, LHRH, LHRH analogs such as buserelin, gonadorelin, naphrelin and leuprolide, GHRH, insulin, heparin, calcitonin, endorphin, TRH, NT-36 (chemical name: N=[[(s)-4-oxo-2-azetidinyl]carbonyl]-L-hystidyl-L-prolinamide), liprecin, pituitary hormones (e.g., HGH, HMG, HCG, desmopressin acetate, etc.), follicle luteoids, .alpha.ANF, growth factor releasing factor (GFRF), .beta.MSH, somatostatin, bradykinin, somatotropin, platelet-derived growth factor, asparaginase, bleomycin sulfate, chymopapain, cholecystokinin, chorionic gonadotropin, corticotropin (ACTH), erythropoietin, epoprostenol (platelet aggregation inhibitor), glucagon, hyaluronidase, interferon, interleukin-1, interleukin-2 menotropins (urofollitropin (FSH) and LH), oxytocin, streptokinase, tissue plasminogen activator, urokinase, vasopressin, ACTH analogs, ANP, ANP clearance inhibitors, angiotensin II antagonists, antidiuretic hormone agonists, antidiuretic hormone antagonists, bradykinin antagonists, CD4, ceredase, CSF's, enkephalins, FAB fragments, IgE peptide suppressors, IGF-1, neurotrophic factors, growth factors, parathyroid hormone and agonists, parathyroid hormone antagonists, prostaglandin antagonists, pentigetide, protein C, protein S, renin inhibitors, thymosin alpha-1, thrombolytics, TNF, vaccines, vasopressin antagonist analogs, alpha-1 antitrypsin (recombinant).
The prior art teach a variety of techniques suitable for controlling transdermal current generators. It should be understood that electrically assisted transdermal delivery of peptides and proteins as well as the phenomenon of electroosmosis, have been disclosed in the prior art. Examples of relevant art includes:
U.S. Pat. No. 3,618,601--teaches automatic control of an iontophoretic current source.
U.S. Pat. No. 4,808,152--teaches an adjustable iontophoretic generator with programmable output.
U.S. Pat. No. 4,141,359--teaches a feedback controlled current source with automatic shutdown in the presence of excessive voltage buildup
U.S. Pat. No. 4,292,968--teaches a an iontophoretic generator which operates in a constant current mode, but which may operate in a constant voltage mode if in the presence of high electrode impedance.
PCT patent application WO 88/08729, teaches an iontophoretic drug delivery system which provides closed loop control of the driving current.
European patent application 0 309 093 EPA--teaches low frequency oscillator for the application of drugs. The device uses a waveform having rapid rise time and a slow fall off time.
U.S. Pat. No. 4,725,263--teaches a programmable constant current source for the transdermal application of drugs.
U.S. Pat. No. 4,406,658--teaches an iontophoretic device for the delivery of drugs. The circuitry includes a current control circuit which ramps the current values in accordance with a timer control circuit.